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Biomedical subjects

L Krause

Publications and source records attributed to L Krause.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of left ventricular mass and geometric remodeling in treated and untreated men and women >50 years of age with systemic hypertension.

To investigate the effects of left ventricular (LV) mass and geometry in hypertensive patients >50 years of age, 540 men and women were divided into controlled, uncontrolled, and untreated groups. The high prevalence of concentric LV hypertrophy in postmenopausal women, despite medical therapy, emerged as a potentially important and underrecognized factor of their cardiovascular risk.

Aged↗
PubMed1997

Disparity between diastolic mitral flow characteristics and left ventricular mass in essential hypertension.

Because left ventricular (LV) hypertrophy and aging have been associated with abnormal LV relaxation, this study evaluated the impact of LV mass on the filling patterns derived by Doppler in a large population aged > or =50 years. Results suggest that in essential hypertension the intrinsic myocardial composition is more important than cardiac hypertrophy in determining LV diastolic properties. This apparent discrepancy between LV mass and diastolic filling patterns highlights the difficulty in establishing the diagnosis of diastolic dysfunction in elderly hypertensives.

Aged↗
PubMed1997

Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study.

BACKGROUND: Tobacco smoking is associated with a higher prevalence of atherosclerosis and respiratory disease. OBJECTIVE: To investigate differences between hemodynamic and biochemical findings in smokers and nonsmokers in the two sexes separately in the Tecumseh population. METHODS: We studied 851 subjects. They were divided according to smoking habits into group 1, nonsmokers (258 men and 234 women); and group 2, smokers (185 men and 174 women). RESULTS: Unpaired Student's t-tests and nonparametric tests were performed to determine the between-group P-values. Only hematocrit differed significantly between smokers and nonsmokers in both sexes (43.9 +/- 0.2 and 44.6 +/- 9.3%, P < 0.05 in men; 39.2 +/- 0.3 and 40.3 +/- 0.3%, P = 0.007 in women, respectively in nonsmokers and smokers). Triglycerides (80.6 +/- 3.8 and 99.6 +/- 4.3 mg/dl, P < 0.001), left ventricular mass index (95.4 +/- 1.9 and 100.0 +/- 1.2 g/m2, P = 0.008), and posterior wall thickness (9.5 +/- 0.1 and 9.71 +/- 0.01 mm, P = 0.044) were elevated and high-density lipoproteins were decreased (48.7 +/- 0.8 and 44.5 +/- 0.9 mg/dl, P < 0.01) only in women smokers. After adjustment for home systolic blood pressure and body mass index the differences in women remained significant except for posterior wall thickness. CONCLUSION: Tobacco smoking is deleterious to both sexes but it appears to be particularly harmful to women. Our data can, in part, explain why the relative risk of myocardial infarction is higher in women than it is in men.

Adolescent↗
PubMed1997

Role of left ventricular hypertrophy in diastolic dysfunction in aged hypertensive patients.

OBJECTIVE: To evaluate the influence of left ventricular hypertrophy (LVH) on the diastolic dysfunction in older hypertensive patients. METHODS: In total 665 patients (58% men, 61% White, aged 55-80 years) with mild-to-moderate essential hypertension underwent Doppler echocardiography. Data included left ventricular dimensions, left ventricular mass index, body mass index, E- and A-wave mitral flow velocities, E:A ratio, deceleration time > 150 ms), impaired relaxation (E:A ratio < 1.0, prolonged deceleration time according to age), and restrictive physiology (E:A ratio > 2.1, deceleration time < 150 ms)]. Data were distributed according to age (50-59, 60-69, and 70-80 years). RESULTS: The overall prevalence of sex-adjusted LVH in this study was 65%. When we compared hypertensive patients with and without LVH, the E- and A-wave velocities, E:A ratio, and deceleration time were similar. Moreover, the prevalences of normal, impaired relaxation, and restrictive physiology patterns among patients with and without LVH did not differ significantly (20, 79.5, and 0.5 versus 24, 75.5, and 0.5%). When the mitral flow patterns were adjusted according to age, the impaired relaxation pattern increased further with age (to 73% during the fifth decade, 83% during the sixth decade, and 88% during the seventh decade). CONCLUSIONS: LVH is not an independent factor associated with abnormal flow patterns in hypertensive patients aged over 50 years with normal systolic contractility. The impaired relaxation is the predominant pattern of diastolic dysfunction in older hypertensive patients and increases further with aging.

Aged↗
PubMed1997

Trends in left ventricular function over three years in the Tecumseh Study.

The relationship between blood pressure and left ventricular diastolic function was examined in participants of the Tecumseh Blood Pressure study. When subjects were divided into three blood pressure groups according to blood pressure levels 3 years apart, it was found that subjects who were had sustained "hypertension" at both time points (SH) had a decreased early/late diastolic filling rate (E/A ratio) compared to subjects who were hypertensive at only one of the timepoints (OH) and those who were consistently normotensive (NN) (1.71 +/- 0.02 NN vs 1.55 +/- 0.05 OH, (p < 0.0001) vs 1.56 +/- 0.07 SH, (p < 0.04)). This relative order was maintained when the second estimation of diastolic filling was performed 3 years later, but the E/A ratio had decreased significantly in all groups (1.54 +/- 0.01 NN vs 1.45 +/- 0.03 OH (p < 0.01) vs 1.37 +/- 0.06 SH (p < 0.006)), consistent with an age-related reduction in diastolic filling. Heart rates were significantly higher in the hypertensive groups initially (63.5 NN vs 66.2 OH (p < 0.03) vs SH 67.3 (p < 0.01)) and increased in all groups over time, with the largest increase in the SH group (64.9 +/- 0.04 NN vs 67.8 +/- 1.02 OH (p < 0.0001) vs 70.9 +/- 1.6 SH (p < 0.01)). Stroke volume index changed in all groups over time, with the increase greatest in the NN group and least in the SH groups the reverse of this pattern was seen for changes in heart rate. All subjects gained weight over the 3 years of the study so that these unexpected changes in stroke volume index and heart rate could be a consequence of a weight gain-related increase in the sympathetic tone, although we have no direct evidence that this is the case. Should this be so, the smaller increase in stroke volume in conjunction with the larger increase in the heart rate in the sustained hypertensive group may reflect the effects of mild blood pressure elevation in producing a reduction in left ventricular diastolic function associated with a decrease in the inotropic responsiveness of the heart to enhanced sympathetic tone.

Adolescent↗
PubMed1996

Mutational analysis of HIV-1 Nef: identification of two mutants that are temperature-sensitive for CD4 downregulation.

The Nef protein of HIV-1 is capable of performing at least two functions: reduction of cell-surface expression of CD4, the viral receptor, and enhancement of HIV-1 infectivity. Here we report the results of assays of CD4 downregulation by nef point mutants. Areas of high charge density and highly conserved sequence motifs were targeted. In general, mutations in the carboxyl-terminal half of the protein had more deleterious effects than did those in the amino-terminal half. A single mutant nef allele was identified which encoded a stable protein but was completely inactive. Two mutant Nef proteins exhibited temperature-sensitive phenotypes in assays of CD4 downregulation.

Amino Acid Sequence↗
PubMed1996

The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid.

BACKGROUND: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating keratoplasty (PKP) and following treatment with cyclosporin A (CsA). METHODS: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n = 24); (ii) operated, CsA-treated (10 mg/kg i.m.; n = 22). Controls were groups (iii) normal LW rats (n = 13); (iv) unoperated, CsA-treated (16 days' treatment; n = 8); (v) anterior perforation of the anterior chamber (n = 3); (vi) eight corneal sutures only (n = 4); (vii) syngeneic operated (LW to LW; n = 4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. RESULTS: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. CONCLUSION: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.

Animals↗
PubMed1996

The behaviour of ED1- and ED2-positive cells in the rat iris and choroid following penetrating keratoplasty and cyclosporin A therapy.

BACKGROUND: The presence, morphology and distribution of ED1 and ED2+ cells have been recently reported in detail in the uveal tissues of the rat. These cells, particularly those of dendritic morphology, are possibly capable of antigen presentation and, therefore, may play an important role in immune processes of uveal and other ocular tissues. Using the whole-mount technique, the distribution of ED1+ and ED2- cells in the rat iris and choroid was investigated following penetrating keratoplasty (PKP) and following treatment with cyclosporin A (CsA). METHODS: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to one of two groups: (I) operated, untreated (n = 24); (II) operated, CsA treated (10 mg/kg i.m.: n = 22). Four groups served as controls: normal LW rats (n = 13); (IV) unoperated, CsA treated (16 days' treatment; n = 8); (V) eight corneal sutures only, representing a simulated or "sham" operation (n = 4); (VI) syngeneic operated (LW to LW: n = 4). Animals of groups I and II were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group I, day 13; Group II, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for ED1+ and ED2+ cells using APAAP immunohistochemistry. RESULTS: In the normal LW rat iris, ED1+ and ED2+ cells of both non-dendritic and dendritic morphology were observed. The placement of sutures in the cornea and PKP with or without treatment resulted in a reasonably regular response in both the iris and the choroid in the operated and partner eye. These included: (a) an increase in round iridal ED1+ and ED2+ cells in the operated eye and in round ED1+ cells in the partner eye; (b) a decrease in dendritiform ED2+ cells in the iris of the operated eyes as well as in the partner eye; and (c) a decrease in the dendritiform ED2+ cells in the choroid of the operated and partner eye. CsA treatment alone in unoperated animals resulted in significant decreases in the number of dendritiform ED1+ cells in the iris and in the dendritiform ED2+ cells in the choroid. CONCLUSION: Corneal transplantation in the Lewis rat results in responses in ED1+ and ED2+ cells in uveal tissues in both the operated eye as well as in the partner eye. The differences in cell behaviour supports the idea that distinct immune-competent cell populations are present within uveal tissues and that they may have differing roles in the pathological eye.

Animals↗
PubMed1996

Flow-cytometric analysis of peripheral lymphocytes in the rat following penetrating keratoplasty and immunosuppressive treatment.

Flow cytometry has been found to be a useful tool in the clinical monitoring of patients following solid organ transplantation. Despite the easier assessibility of corneal graft acceptance or rejection, flow-cytometric evaluation of peripheral lymphocytes following systemic immunosuppression is important in the evaluation of therapeutic efficacy. The systemic effect of penetrating keratoplasty (PKP) and of immunosuppression with cyclosporin A (CsA), leflunomide (LF), and the nondepleting anti-CD4 antibody, RIB 5/2, on peripheral lymphocytes was investigated in the rat model. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA, 10 mg/kg; (3) LF, 10 mg/kg; (4) LF, 5 mg/kg; (5) LF, 2.5 mg/kg; (6) LF, 10 mg/kg; combined with CsA, 10 mg/kg; and (7) RIB 5/2, 4 mg/kg, combined with CsA, 1.5 mg/kg. Controls included the following groups: (8) unoperated, CsA-treated at 10 mg/kg; (9) unoperated, LF-treated at 10 mg/kg; (10) unoperated, LF-treated at 10 mg/kg and CsA-treated at 10 mg/kg; (11) unoperated, RIB 5/2-treated at 4 mg/kg and CsA-treated at 1.5 mg/kg; (12) syngeneic grafts; and (13) normal Lewis rats. Cells from blood and spleen samples were enriched using Ficoll density centrifugation, and lymphocytic surface markers CD 3, CD 4, CD 8, and RT 1b (Ia) were analyzed by direct immunofluorescence using flow cytometry. In the untreated allogeneic PKP, a decrease in the percentage of serum CD 3+, CD 4+, CD 8+, and CD 4+ RT 1b+ lymphocytes was apparent from the 5th to the 9th postoperative day. At corneal graft rejection, a normalization of serum CD 3+ and CD 4+ levels occurred, whereas the percentage of serum CD 8+ lymphocytes remained slightly raised. Significantly enhanced decreases in levels of CD 4+ lymphocytes were observed following treatment with CsA, LF, and, particularly, therapy with RIB 5/2 and a subtherapeutic dose of CsA. Concomitant decreases were also apparent following treatment with CsA or LF. In contrast, the combination of RIB 5/2 and CsA (1.5 mg/kg) resulted in a reactive increase in levels of CD 8+ lymphocytes as well as an increased expression of RT 1b by the remaining CD 4+ lymphocytes. The latter alterations corresponded to indefinite acceptance of the corneal grafts, which was observed only in the animals treated with RIB 5/2 and CsA. PKP in the rat model is accompanied by alterations in peripheral lymphocytes. Additional influences are exerted by immunosuppressive therapy, with the most specific and predictable alterations being achieved with anti-CD4 monoclonal antibody therapy.

Animals↗
PubMed1995

Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.

Anti-CD4 monoclonal antibodies (mAbs) have been shown to inhibit in vitro T-cell activation and proliferation to both antigens and mitogens. Animals studies have demonstrated the immunosuppressive potency of anti-CD4 mAbs given in vivo for therapy of autoimmune disease and following allografting. Similarly, leflunomide (LF), a new potent immunosuppressive, has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplant rejection. LF is thought to antagonize cytokine activity, thereby interfering with T-helper-cell-dependent B- and T-lymphocyte proliferation. A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA at 1.5 mg/kg; (3) RIB 5/2 at 2.5 mg/kg; (4) RIB 5/2 at 2.5 mg/kg and CsA at 1.5 mg/kg; (5) RIB 5/2 at 2.5 mg/kg, CsA at 1.5 mg/kg and LF at 10 mg/kg; (6) RIB 5/2 at 4 mg/kg; (7) RIB 5/2 at 4 mg/kg and CsA at 1.5 mg/kg; and (8) RIB 5/2 at 4 mg/kg, CsA at 1.5 mg/kg, and LF at 10 mg/kg. RIB 5/2 was given intraperitoneally at 24 h before surgery, on the day of grafting, and on postoperative day 1 and was continued every 2nd day until the rat had received ten doses in all (postoperative day 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Leflunomide therapy following penetrating keratoplasty in the rat.

BACKGROUND: The isoxal derivative, leflunomide (LF), is a new potent immunosuppressive which has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplantation rejection. LF is thought to antagonise cytokine activity and thereby to interfere with T-helper-cell-dependent B- and T-lymphocyte proliferation. METHODS: We used LF to treat corneal allograft rejection in the rat, comparing its effect with that of cyclosporin A (CSA). Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: I, untreated; II, CSA (10 mg/kg i.m.); III, LF (2.5 mg/kg p.o.); IV, LF (5 mg/kg p.o.); V, LF (10 mg/kg p.o.); VI, combined therapy (LF 10 mg/kg p.o. and CSA 10 mg/kg i.m). Treatment began on the first postoperative day and was continued until rejection occurred. RESULTS: The mean graft rejection time in the untreated allogeneic group was 12 days. A significant delay in graft rejection was observed in all treatment groups compared with group I (P < 0.001). Further, the delay in graft rejection resulting from combined therapy (group VI) was statistically significant compared with all other groups (P < 0.001). CONCLUSION: These results suggest that (a) LF when used alone is as effective as CSA in treating corneal allograft rejection in the rat, and (b) when LF and CSA are combined they are more effective than either drug alone in the prolongation of allograft survival.

Administration, Oral↗
PubMed1994

The effect of hypertensive episodes and cardiac hypertrophy on the canine cardiac baroreflex.

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean +/- s.e.m.) was 116.0 +/- 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 +/- 8.1 g (P = 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 +/- 0.06 at baseline to 1.54 +/- 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the 'steady-state' drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 +/- 0.43 beats/min per mmHg at baseline to 3.10 +/- 0.45 beats/min per mmHg (P = 0.067) after 6 weeks of compression. This gain reduction became significant after beta-adrenoceptor blockade with propranolol (3.13 +/- 0.55 vs 2.32 +/- 0.25 beats/min per mmHg; P = 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r = 0.96; P < 0.001) during the 6 week compression period.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Sex-specific determinants of increased left ventricular mass in the Tecumseh Blood Pressure Study.

BACKGROUND: Left ventricular hypertrophy (LVH) defined by either ECG or echocardiographic criteria is a risk factor for cardiovascular morbidity and mortality. A number of determinants of LVH have been described in previous studies, principally male sex, hypertension, obesity, and aortic valvular stenosis. We examined the distribution of LV mass (LVM) in a population of 18- to 42-year-old normotensive men and women who were free of valvular heart disease to establish sex-specific normal values for LVM index (LVMI) and to determine the correlates of LVMI. METHODS AND RESULTS: LVM was derived from measurements obtained by M-mode echocardiography. Average LVMI is significantly greater in men (102.9 +/- 0.7 g/m2) than women (88.2 +/- 0.7 g/m2). By defining LVH as an LVMI greater than the 90th percentile, we developed sex-specific criteria for LVH: men, > 125.4 g/m2; women, > 110 g/m2. We found that LVH in men is associated with indices of enhanced sympathetic nervous system reactivity and with elevated fasting insulin and triglyceride levels, which may be caused by insulin resistance. In women, LVH was associated with higher body weight and obesity. CONCLUSIONS: Before the onset of hypertension, increased LVMI appears to have different determinants in men and women. We suggest that early LVH in young men is a manifestation of hyperkinetic borderline hypertension, a state previously shown to be associated with increased sympathetic nervous system activity and insulin resistance. The hyperkinetic state is less prevalent in young women, in whom increased adiposity seems to be the predominant factor associated with LVH.

Adult↗